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Biomedical subjects

J P Reynier

Publications and source records attributed to J P Reynier.

At least 19 recordsLinked to original sources

The preparation of orally disintegrating tablets using a hydrophilic waxy binder.

The demand for rapidly disintegrating tablets (RDT) has been growing during the last decade especially for elderly and children who have swallowing difficulties. The problem of certain RDT is their low physical resistance and high friability. This work describes a new approach to prepare RDT with sufficient mechanical integrity, involving the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate). Superpolystate is a waxy material with a melting point of 33-37 degrees C and an HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues. The incorporation of Superpolystate in the formulation of RDT was realised by means of two different granulation methods: wet granulation by using an emulsion of this waxy binder as granulating liquid and melt granulation where the molten form of the binder was used. Granule size distributions of both wet and melt granules of crystallised Paracetamol and D-mannitol were compared using laser light diffractometer. Scanning electron microscopy (SEM) was used to examine their morphological characteristics. The potential of the intragranular addition of croscarmellose sodium as a disintegrating agent was also evaluated. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of croscarmellose sodium. An improvement in tablet hardness and friability was observed with both granulation methods where we were able to obtain RDT with a disintegration time of 40 +/- 2 s and a hardness of 47.9 +/- 2.5N.

Acetaminophen↗

Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.

BACKGROUND & AIMS: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. METHODS: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM). RESULTS: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. CONCLUSIONS: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.

Acidosis↗

Texture optimization of water-in-oil emulsions.

The aim of this research is to demonstrate the effect of variations in certain parameters of the oily phase (OP) in water-in-oil (W/O) emulsions on rheological and texture properties of finished products. The formulated emulsions were selected according to an optimal experimental procedure. The applied variations were nature of the OP, its volume fraction, the hydrophilic-lipophilic balance (HLB) value, and the surfactant proportion. Results are presented for the followed tests carried out on the emulsions: texture analysis, rheology, and particle size analysis. The oils used in the study were sweet almond oil, liquid paraffin, maize oil, cyclomethicone, dimethicone, and wheat germ oil. The resulting data demonstrate a notable influence of the volume fraction oil on hardness, viscosity, adhesiveness, and cohesiveness of W/O emulsions. Emulsion hardness and viscosity increased as the OP percentage increased; this effect being even more pronounced for the vegetable oils. In contrast, emulsion adhesiveness and cohesiveness decreased as the volume fraction oil increased. The HLB value of the surfactant mixture of the emulsion also influenced hardness, adhesiveness, and elasticity, increasing or decreasing as HLB value did.

Drug Compounding↗

Hyperkalemia risks in hemodialysed patients consuming fluoride-rich water.

In order to observe the consequences of chronic ingestion of high fluoride-rich water on plasma potassium levels of hemodialysed subjects, we have conducted a retrospective study on 25 patients with chronic renal failure, treated with a substitute method, six of whom (consumers group, group C) were drinkers of a bicarbonate (about 4500 mg/l) and fluoride-rich (9 mg/l) mineral water, the Vichy Saint-Yorre water. With respect to sodium polystyrene sulfonate consumption (n = 17), there was no significant difference between group C and NC (non-consumers group). A significant correlation between plasma fluoride and potassium levels was observed only before dialysis (P < 1 x 10(-7)) but not after dialysis. A group by group analysis revealed that this correlation was linked to group C (P < 5 x 10(-6)), in which kalemia before dialysis was higher than that observed in group NC (P < 0.005). Moreover, it appeared that the higher fluoride levels were, the higher the kalemia was inclined to be. Thus, the risks of hyperkalemia in dialysed patients, who also drink Vichy St-Yorre water or other fluoride-rich waters, are more important, while not forgetting the risk of fluorosis. The mechanisms by which chronically administered fluoride could increase kalemia are also discussed.

Adult↗

Controlled-release behavior of diphenhydramine hydrochloride loaded neutral microgranules and coated using ethylcellulose water dispersion.

The development of a loading method of a water-soluble drug using aqueous binding solution to produce microgranules that were then coated with an aqueous ethylcellulose dispersion to sustain drug release is described. The results, in terms of drug used, showed that besides the fluidized bed parameters, the amount of drug dissolved in the binder solution plays an important role in obtaining a satisfying result during the spraying process. Thus, it seems necessary to determine the critical concentration above which the material started to adhere to the interior of the fluidization column, and the possibility of drug layering onto carrier material is aggravated. ANOVA of the time parameter for release of 63.2% of total drug (td) value showed significant influence of ethylcellulose (Aquacoat ECD-30) and dibutyl sebacate concentration on diphenhydramine hydrochloride (DPH) release. The dissolution rate decreased with an increase in polymer concentration. The diffusional exponent n of the Peppas equation indicated that the DPH release kinetic was non-Fickian but approached Fickian diffusion, particularly at higher coating levels.

Cellulose↗

Comparative tablet and rheological properties of new microcrystalline cellulose: direct compression and wet granulation methods.

The overall objective of this study was to compare the rheological properties and tablet characteristics of two new varieties of celluloses (Vivacel 101 and 102), recently produced and commercialized, with the classical varieties of celluloses (Avicel and Elcema). The results showed no significant differences in the rheological properties of Vivacel and Avicel, while significant differences were found between the two celluloses and Elcema. Furthermore, there were no statistically significant differences in the disintegration times and Td values of Vivacel and Avicel. In conclusion, it was found that these new celluloses offer all the known advantages of Avicel.

Cellulose↗

Release of benzimidazole and benzylidene camphor from topical sunscreen formulations.

Absorption of two ultraviolet (UV) filters was evaluated through a lipophilic synthetic membrane (Folioxane) and excised hairless rat skin using a flow-through diffusion cell. Folioxane membrane is an artificial skin used in the treatment of third-degree burns. Diffusion tests were performed with aqueous solutions and galenic formulations (one water-in-oil [W/O] emulsion and two oily gels). Analyses were achieved with high-performance liquid chromatography (HPLC) with UV detection at 295 nm. Diffusion kinetics of 17 beta estradiol, a reference compound, through rat skin, human skin, and Folioxane membrane were performed to validate the in vitro model. Phenylbenzimidazole and methylbenzylidene camphor in aqueous solutions were diffused at a regular rate through the Folioxane film. The release of phenylbenzimidazole was very slow, whereas the release of benzylidene camphor was more pronounced: a decrease of the quantity was observed in the donor compartment (30% at 6 hr and 93% after 72 hr). A significant flow of benzylidene camphor was also measured through excised skin of rat in the first 3 hr. The skin absorption was 38% over 72 hr. The W/O emulsion had low penetration of UV filter: 20% of the initial amount for Folioxane membrane and 0.4% for rat skin. In contrast, the penetration of two oily gels was identical: 28% on Folioxane membrane and 0.6% on rat skin. This study demonstrates the transcutaneous diffusion of two important classes of sunscreens through a lipophilic Folioxane membrane and through excised hairless rat skin. From the results, Folioxane membrane appears to be an alternative model for studying diffusion of topical molecules and as a tool for guiding formulation choices.

Administration, Topical↗

Investigation of fluoride elimination during a dialysis session.

We have conducted a study of the elimination kinetics of fluoride ions by a log linear regression analysis of plasma levels obtained during a bicarbonate hemodialysis session, with a dialyzer in polymercaprin for six patients with chronic renal failure. Using plasma fluoride levels of 35 patients studied for 20 months, we have validated these kinetics for hemodialysis with sodium bicarbonate, acetate-free biofiltration, hemodiafiltration with low flow rate and other dialyzers. Our results show that the decrease in plasma fluoride levels is statistically significant only after the first hour, and the fall reaches approximately 30% after a 4 h dialysis session. We propose that post-dialysis measurements of plasma fluoride are now not necessary if levels before dialysis are known.

Adult↗

Long-term follow up of ionic plasma fluoride level in patients receiving hemodialysis treatment.

The elimination half-life of fluoride is significantly increased in patients with chronic renal failure. This led us to conduct a study of variations of its plasma levels in 35 patients receiving dialysis treatment. In this population, there is a gaussian distribution of the values before and after the hemodialysis session, with a significant decrease in the averages. Furthermore, there is a highly significant correlation between fluoride levels before and after the dialysis session (P < 0.00001), and also between the amount of time in hemodialysis (in months) and the average fluoride level before dialysis (r = 0.624; P = 0.008). The presence of a group of patients consuming fluoride waters such as Vichy St-Yorre Water was easily identified by their excessive fluoride levels (above 100 micrograms/l), which could have a tendency to increase the risks of this group.

Adult↗

Protein synthesis measurement in cancer patients with 13C valine.

The flooding dose technique is a method that uses tracer amino acids to measure the rate of protein synthesis in tissues in vivo. This technique involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize difference in isotopic enrichment of the free amino acid in plasma and tissue compartments which represent the precursor pool of protein synthesis. Seven patients with localized colorectal carcinoma received a total parenteral nutrition before surgery and protein synthesis was measured in tumour and colon after administration of a large dose of valine (20% atom percent excess). The enrichment of free valine in plasma and tissues was measured by GCMS and the enrichment of protein-bound valine into tumour and colon by IRMS. The fractional synthesis rate in tumours was 13.44 +/- 6.9%/day compared to a value of 10.9 +/- 8.1%/day in healthy colon. The lack of significant difference probably relates to the low number of patients and the variability of protein synthesis rate in tumours.

Aged↗

Splanchnic acid-base status and urea metabolism in uremic rats.

Acidosis may alter hepato-splanchnic amino acid metabolism during uremia.26 uremic rats and 30 controls were studied for portal and arterial acid-base balance and urea synthesis during enteral nutrition. Uremic rats exhibited increased (p < 0.05) portal H(+) (47.20 +/- 0.018 vs 43.05 +/- 0.49 nmol/I) and decreased HCO(3)(-) (19.45 +/- 0.69 vs 23.01 +/- 0.57 mmol/l) without significant change in arterial H(+) (45.29 +/- 1.13 vs 43.15 +/- 0.49) and HCO(3)(-) (18.41 +/- 0.64 vs 19.59 +/- 0.49). Porto-arterial difference showed an intestinal HCO(3)(-) release in controls only (3.53 +/- 0.64 mmol/l). Urea synthesis rate was significantly enhanced by enteral nutrition in controls only: 54.33 +/- 17.3 vs -11.8 +/- 20 micromol/min 100g body mass. Thus, during uremia, portal acidosis was associated with a decrease in enteral nutrition-induced urea synthesis.

Journal Article↗

Isolated rat hepatocyte metabolism is affected by chronic renal failure.

Metabolic changes due to chronic renal failure (CRF) were studied in isolated liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by the Berry and Friend method and incubated with various substrates in order to study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as cytosolic and mitochondrial adenine nucleotide content. CRF rat hepatocytes exhibited a 25% to 45% decrease in gluconeogenesis and ureagenesis (P < 0.05) from all the tested substrates (lactate plus pyruvate, fructose, glycerol, dihydroxyacetone, alanine and glutamine for gluconeogenesis and alanine, glutamine, ammonia and ammonia plus ornithine for ureagenesis), while endogenous rates were unaffected. CRF did not alter ketone body production (acetoacetate and beta-hydroxybutyrate) from oleate or octanoate. In the presence of either oleate, lactate plus pyruvate or ammonia, oxygen uptake as well as cytosolic and mitochondrial total adenine nucleotides were unaffected by CRF, while the mitochondrial ATP/ADP ratio decreased (P < 0.001). Thus, this study of hepatocyte intermediary metabolism during CRF showed an alteration of only gluconeogenesis and ureagenesis pathways. Moreover, the association of normal oxygen uptake together with decreased mitochondrial ATP/ADP ratio suggest a possible increase in hepatocyte ATP demand during uremia.

Adenine Nucleotides↗

Plasma concentrations after three different doses of topical isotretinoin.

The aim of the study was to investigate the plasma concentrations of isotretinoin and its metabolites, at three doses and after single and multiple topical applications of isotretinoin gel (0.05%) in hairless rats. We used a highly sensitive HPLC method for simultaneous determinations of these compounds, with a detection limit of 2 ng/ml in plasma. Isotretinoin and its metabolites were detected after single and multiple cutaneous applications of overdosing (2,000 mg) of isotretinoin gel up to 24 h after the single dose and after the last dose. The plasma concentrations of these compounds were below the limit of quantification in all the animals at all times for the 200- and 20-mg doses.

Administration, Topical↗

Using ultrapure water in hemodialysis delays carpal tunnel syndrome.

Since 1977, our patients have undergone chronic HD with ultra-pure dialysate (UPD), defined as having endotoxin levels below 0.008 ng/ml and less than 1 bacteria/ml of dialysate. We evaluated the incidence of carpal tunnel syndrome (CTS) in three groups of patients. Group I (GI), 84 patients, dialysed for 6.1 +/- 3.2 years (mean +/- SD) with UPD only; Group II (GII), 39 patients, first dialysed for 3.7 +/- 2.3 years with non-UPD and afterwards for 8.4 +/- 2.1 years with UPD; Group III (G III), 103 patients treated for 6 +/- 5.9 years exclusively with non-UPD. All patients were dialysed with cuprophan or cellulose acetate membranes. Results, expressed by Kaplan-Meier actuarial survival curves as the percent of patients without CTS, show that CTS occurred significantly less in GI than in GIII. This may be due to less stimulation of monocytes resulting from the absence of bacteria, endotoxins and pyrogens in the dialysate, which would reduce the stimulation of cytokines release, interleukin 1 and 6, and tumor necrosis factor, known to stimulate beta 2 microglobulin synthesis.

Actuarial Analysis↗

[Urinary calculi. Current role of in situ dissolution].

The two cases reported here illustrated the advantages of urinary stone dissolution in situ. One patient had bilateral urate calculus with anuria; the other had recurrent staghorn calculus. In both cases a nephrostomy stent was installed percutaneously and the calculi were dissolved by irrigation.

Female↗

[Plasma and intra-erythrocytic concentrations of copper and zinc in uremic patients treated by periodic hemodialysis].

In this report, the authors have studied the plasma and red blood cell concentrations of both zinc and copper in 90 uremic patients treated by intermittent hemodialysis. They found that plasmatic and erythrocytic levels of zinc together with the copper red blood cell concentrations determined before and after the hemodialysis are not significantly different from these recorded on normal subjects. However, the plasmatic copper concentrations are markedly increased, although no relevant correlation between the determined values and those measured in the dialysis bath can be drawn. Plasmatic copper levels fluctuations have been followed on 5 patients during an hemodialysis period ranging from 4 to 36 months, and did not reveal any relevant increase of copper levels. The etiology of the plasmatic copper concentration still be remain to be determined.

Adult↗